tbuckley/cabot-search huggingface dataset:
Multimodal interventions targeting identified barriers to improve lung cancer screening in northeast Georgia.
Authors: Swathi Kanakamedala, Shivang Danak, Andria P Caton
Journal: Journal of Clinical Oncology (2023)

6570 Background: Lung cancer is the leading cause of cancer deaths with over 50% of patients diagnosed at an advanced stage. Lung cancer screening (LCS) guidelines were recently updated in 2021, which expanded the age group and reduced the pack years, and thereby increased eligibility. However, the underutilization of low dose computed tomography (LDCT) scans is seen nationwide. In 2015, the National Health Interview Survey found that only 3.9% of eligible adults underwent LCS. The barriers for LCS identified in national literature included failure of electronic medical records (EMR) to notify providers of eligible patients, lack of insurance coverage, patient refusal, and lack of patient and provider awareness. This quality improvement project was performed to improve LCS in primary care clinics (graduate medical education [GME] and non-GME) at a tertiary medical center in northeast Georgia by addressing these barriers. Methods: In GME clinics, the goal was to double LDCT scans from 14 to 28 monthly. In non-GME clinics, the goal was to increase LDCT scans by at least 50% from 28 to 42 weekly. LDCT scans performed between January 1st to May 31st 2022 was used as baseline data. The interventions spanned over six months, from June 1st to November 30th 2022. Multimodal interventions were used to target various barriers. Accurate tobacco history in the EMR was improved by participating in the nationwide Just Ask Campaign. Flyers posted in clinics provided information on current guidelines and a QR code for patients to determine their LCS eligibility. Provider reference guides highlighted LCS guidelines and billing codes. Community events and social media were used to spread LCS awareness. Results: During the implementation phase, the average monthly LDCT scans increased to 23 scans in GME clinics and 40 scans weekly in non-GME clinics. In GME clinics, the goal of 28 scans monthly was achieved in one out of six months. In non-GME clinics, the goal of 42 scans weekly was surpassed in four out of six months. The Long-Range Acoustic Device (L-RAD) scoring system helped diagnose three cancers in the GME clinics and about one cancer for every 10 L-RAD4 in non-GME clinics. The baseline period LDCT scans of 78 (GME) and 656 (non-GME) increased to 177 (GME) and 1109 (non-GME) during the intervention period. Conclusions: This multimodal approach in addressing known barriers to increase LCS across primary care clinics in a single healthcare system is feasible and was associated with short-term improvements. Although the targets were not met every month, there was a notable improvement during the intervention period. A major limitation was the inability to determine which intervention had the greatest impact. A newly identified barrier was the lack of follow up scans being ordered by providers. This project demonstrates the potential to increase LCS using a multimodal approach, which can be implemented in similar healthcare systems.
Lenalidomide-based monotherapy versus augmented therapy for maintenance in standard risk multiple myeloma patients with no complete response post autologous hematopoietic cell transplantation.
Authors: Hussein Awada, Adel Hajj Ali, Chadi Tabaja, Jack Khouri, Faiz Anwer
Journal: Journal of Clinical Oncology (2023)

8055 Background: Standard risk (SR) multiple myeloma (MM) is typically characterized by the absence of poor prognostic cytogenetic aberrations, and better outcomes. However, outcomes in SR MM remain far from homogeneous, especially in patients undergoing autologous hematopoietic cell transplant (AHCT). While many patients do well initially, relapse is inevitable. Here, we studied the role of lenalidomide (R) maintenance therapy in determining outcomes in SR MM with no complete response (non-CR) post-AHCT. Methods: We retrospectively reviewed all MM patients who underwent AHCT at the Cleveland Clinic between January 1, 2011 and January 15, 2021. Electronic medical charts were accessed to retrieve data on demographic characteristics, comorbidities, International Scoring System (ISS) staging, cytogenetic risk categorization, serum and bone marrow studies, as well as maintenance therapy. SR MM was considered in patients who did not have t(4;14), t(14;16), t(14;20), del(17p), or gain(1q). Remission status was determined by serum studies at 3 months post-AHCT. The primary endpoint was median time to either progression or death, reported as time to event (TTE) determined by Kaplan Meier analysis. Results: A total of 517 patients were reviewed, of whom 279 were determined as SR MM. Further stratification yielded 100 non-CR SR patients on lenalidomide-based maintenance, of whom 87 were on R monotherapy and 13 on R combination. Comparison between the R-monotherapy and combination groups showed similar age at AHCT (60.5 vs 56 years, P=0.07), time to transplant (23.5 vs 30.8%, P=0.7), albumin levels (&lt;3.5 g/dL 25 vs 25%, P=1), Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score (≥3 43.5 vs 30.8%, P=0.5), Male preponderance (58.8 vs 69.2%, P=0.6), ethnicity (White 82.4 vs 76.9%, P=0.7), ISS stages (I 41 vs 45.5%, II 41 vs 36.4%, III 17.9 vs 18.2%, P=0.9), pre-AHCT lines of therapy (≥2 31.8 vs 38.5%, P=0.8), and pre-AHCT bone marrow plasma cells (≥10%:9.5 vs 7.7%, P=1), respectively. The only significant difference between the two groups was in the MM immunoglobulin subtype (IgG 80 vs 50%, P=0.02). Kaplan-Meier analysis for median TTE revealed that the R monotherapy group had a significantly shorter median TTE at 38.1 months versus 68.6 months (P=0.03) for the R combination group. Conclusions: SR MM patients who do not achieve a CR post-AHCT have better outcomes with R-combination rather than monotherapy.
Genomic characterization of papillary thyroid carcinoma in Chinese Shandong population.
Authors: Xungeng Li, Licheng Du, Jiyu Li, Luming Zheng, Jun Zhang, Yongjie Sun, Ming Qi, Xingchen Shang, Shunchao Yang, Jialiang Xing, Meng Wang, Ke Han, Chuang Liu, Ling Li
Journal: Journal of Clinical Oncology (2023)

e18085 Background: With the emergence of mutation-based diagnosis and therapies for patients with papillary thyroid carcinoma (PTC), molecular profiling has become an important component of care. Although next-generation sequencing (NGS) gene panels are accessible to clinicians, the key genetic alterations of PTC in Chinese Shandong population were rarely descripted. Methods: A total of 127 papillary thyroid carcinoma patients were enrolled in this cohort, including 49 (38.6%) males and 78 (61.4%) females from January 2020 to May 2022. The median age were all 48 years. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues were all collected and analyzed from these patients. Somatic and germline mutations were identified including 38 genes associated with tumor development. Sequencing data were analyzed to call tumor specific single nucleotide variants (SNV), small insertions and deletions (InDels), copy number alterations (CNA), gene fusions and rearrangements. Results: A total of 117 out of 127 papillary thyroid carcinoma were NGS-positive (92.1%), with a high prevalence of BRAF V600E mutations (52.0%, 66/127) and MLH1 mutations (23.6%, 30/127), and a low prevalence of RAS mutations (10.2%, 13/127)， ROS1 (9.4%, 12/127). Overall, 257 somatic mutations including 249 SNVs (6 splicing, 4 stopgain, 4 frameshift，and 235 nonsynonymous), 3 fusions, 3 deletions, and 1 insertions in 38 genes were identified in the PTC samples. Gene fusions, involving the RET and NTRK1 genes, were identified in three PTCs (2.4%), including NTRK1-TPM3, NTRK1-SQSTM1 and CCDC6-RET. And the three fusions patients were all BRAF V600E-negative cases. Furthermore, in our cohort, BRAF V600E mutation carriers also owned other actionable, the most frequent one was MLH1 (34.8%), followed by RET (15.2%), ROS1 (10.6%), and ATM (10.6%). We also found that three PTC patients carried germline variants of uncertain significance, including ATM (p.L857P), MET (p.L211W) and RET (p.C515R), which are heterozygous mutations. Conclusions: We described the distinct molecular profile in the Chinese Shandong population with PTC. Most patients had at least one potentially actionable mutation, predominantly driven by BRAF V600E and MLH1 alterations. These findings may help in moving toward the more comprehensive and effective personalized treatment of papillary thyroid carcinoma in Chinese.
Effects of [<sup>177</sup>Lu] Lu-PSMA-617 on overall survival in TheraP versus VISION randomized trials: An exploratory analysis.
Authors: Yu Yang Soon, Ian Marschner, Michael S Hofman, Louise Emmett, Ian D. Davis, Martin R. Stockler, Andrew James Martin
Journal: Journal of Clinical Oncology (2023)

5045 Background: Observed effects on overall survival (OS) differed in the first two randomized trials (RCTs) of [ 177 Lu] Lu-PSMA-617 (LuPSMA) in metastatic, castration-resistant prostate cancer. TheraP randomized participants to LuPSMA or Cabazitaxel (CBZ). In TheraP, the CBZ group (n = 101) included 20 participants who crossed over to LuPSMA, and the LuPSMA group (n = 99) included 32 who crossed over to CBZ. VISION randomized participants to treatment with or without LuPSMA, plus physicians’ choice among protocol-defined treatments, excluding CBZ. Thirty-eight percent of control group participants in VISION had received CBZ prior to randomization. This study investigated explanations for differences in these RCTs in the observed effects of LuPSMA on OS. Methods: Individual participant data (IPD) on survival time from VISION was extracted from published survival curves for comparison with IPD from TheraP. Rank-preserving structural failure time (RPSFT) and inverse probability of censoring weighting (IPCW) were used in TheraP to estimate treatment effects on OS in counterfactual analyses assuming crossover had not occurred in either group, or in both groups. Results: OS was longer in the comparator group of TheraP than the comparator group of VISION (HR: 0.57, 95% CI 0.43 - 0.75) while OS was similar in the LuPSMA groups of VISION and TheraP (HR: 0.92, 95% CI 0.70 - 1.19). No significant differences in OS between the LuPSMA and CBZ groups of TheraP were apparent using counterfactual analyses assuming crossovers had not occurred (No crossover from CBZ: RPSFT HR 0.97, 95% CI 0.62 –1.52, IPCW HR 0.92, 95% CI 0.65-1.32; No crossover from LuPSMA: RPSFT HR 0.97, 95% CI 0.60–1.58, IPCW HR 0.82, 95% CI 0.55–1.24; No crossover from LuPSMA or CBZ: RPSFT HR 0.97, 95% CI 0.53-1.74, IPCW HR 0.82, 95% CI 0.53–1.27). Conclusions: The difference in observed effects of LuPSMA on overall survival in TheraP and VISION are better explained by the use of different comparator treatments in their control groups than by crossovers in TheraP from Cabazitaxel to LuPSMA, or LuPMSA to Cabazitaxel. Clinical trial information: NCT03392428 , NCT03511664 .
Gastric gastrointestinal stromal tumors and overall survival in elderly patients.
Authors: Asha Spitzer, Hyunjee V. Kwak, Amber Chang, Peter D Peng, George Kazantsev, CK Chang
Journal: Journal of Clinical Oncology (2023)

e23516 Background: The purpose of this study is to analyze the overall survival (OS) of various age groups of patients diagnosed with gastric gastrointestinal stromal tumors (GIST). Methods: We compared 4 different age groups ( &lt; 50 years old, 50-64 years old, 65-79 years old, and 80 or greater) comprising 230 patients in terms of various clinicopathological parameters and OS from January 2010 to December 2020 within Kaiser Permanente Northern California (KPNC), using Kaplan-Meier curves, and Cox proportional hazard regression model. Results: Univariate analysis showed that mitosis greater 10 HPF was a statistically significant predictor of decreased OS from gastric GIST (p = .032). Although necrosis alone was not significant (p = .271), the combination with higher mitotic rate was significant (p = .025). Octogenarians with gastric GIST were more likely to present with bleeding, with a 5.3% ninety-day surgical mortality rate. Multivariate Cox regression showed that patients 80 years of age or greater had decreased OS when compared to the other age groups ( p= .002). Conclusions: Gastric GIST mitotic rate is significant in term of overall survival across all age groups and the combination with necrosis portends decreased overall survival. Patients over 80 have a decreased overall survival and require additional vigilance in the early peri-operative period.
Mechanisms of sensitivity to platinum-based chemotherapy in PD-1 blockade-refractory head and neck cancer.
Authors: Kyunghee Burkitt
Journal: Journal of Clinical Oncology (2023)

e18003 Background: Our clinical observation from recurrent/metastatic head and neck patients who treated with platinum based combination after progression on pembrolizumab showed a striking response rate of 80% (8 out of 10 patients), this impressive ORR is dramatically higher than the historical ORR of 27% in the first-line setting. Our mouse model of ‘immune-cold’ head and neck cancer is developed to investigate the mechanism of sensitivity to platinum- based chemotherapy in PD-1 blockade-refractory head and neck cancer. Methods: For ‘immune-cold’ syngeneic model of HNSCC, C57BL/6 mice were injected with 5 × 10 4 MOC2 tumor cells in the right flank. After 11 days, mice with palpable tumors were randomized and treated concurrently with 4 groups (n = 5 per group): control, anti–PD1 antibody (200 mcg three times/week × 3 cycles), cisplatin (3mg/kg) +paclitaxel (5mg/kg) once a week x 3 cycles, or anti-PD1 antibody (200 mcg three times/week × 1 cycle) followed by cisplatin (3mg/kg) + paclitaxel (5mg/kg) once a week x 2 cycle. Cisplatin + paclitaxel arm received total of 4 cycles of treatment, while PD-1 followed by cisplatin and paclitaxel arm received total of 3 cycles of cisplatin and paclitaxel, this schedule was set up to maintain every 3 week regimen with same duration of treatment time to mimic patient’s treatment schedule in clinic setting. Tumor volume was measured 3 times per week. Results: Our initial pilot mouse model study showed similar tumor response seen in patient population. Starting on D24, average tumor size of PD1 inhibitor followed by cisplatin+paclitaxel group is significantly decreased compared to PD1 inhibitor or cisplatin+paclitaxel group and the difference is statistically significant. Most of mice in control and PD1 inhibitor group died at day 24 due to tumor progression. Our IHC data showed that the expression levels of immune markers such as CD8+, CD4+ and PDL1 in tumors treated with PD1 inhibitor followed by cisplatin and paclitaxel were increased, compared to almost no or scant expression (CD8+, CD4+) and lower expression (PDL1) in tumors treated with cisplatin and paclitaxel alone. With our expansion cohort, we will be further exploring key changes in immune signatures using both peripheral blood samples and tumor blocks for flow cytometry (myeloid/lymphoid subtypes, alterations in cytokine expression and circulating tumor DNA levels) and RNA sequencing analysis. Conclusions: We successfully established an ‘immune-cold’ mouse model of head and neck and reproduced similar tumor response seen in clinic. Preliminary data showing increased expression of immune makers such as CD8+, CD4+ and PDL warrants further investigation on tumor immune microenvironment remodeling as a potential mechanism of sensitivity to platinum-based chemotherapy in PD-1 blockade-refractory head and neck cancer.
Evaluation of outcomes between rituximab-abbs and reference product rituximab in adult patients with newly diagnosed diffuse large B-cell lymphoma in a non-inferiority study.
Authors: Vivian Nguyen, Helen Wong, Timothy Mok, Merta Cushing, Michael Lam, Stephanie Lai-Ting Ho, Lisa Y. Law, Ashraf R. Aziz, Fang Niu, Rita L. Hui
Journal: Journal of Clinical Oncology (2023)

7556 Background: Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard of care for diffuse large b-cell lymphoma (DLBCL). However, adding rituximab has increased treatment costs. Thus, development of biosimilars help provide more affordable care. Though rituximab-abbs was studied primarily in the follicular lymphoma population, in 2018 the FDA approved this drug as the first biosimilar for all indications of the reference product based on extrapolation. However, there are no clinical trials studying the effectiveness and safety of rituximab-abbs in DLBCL in the U.S. Methods: This is a data-only, non-inferiority study to compare two-year overall survival (OS) and the incidence of serious adverse events (AEs) between rituximab-abbs and its reference product (RP) as R-CHOP among adult patients with newly diagnosed DLBCL, with an index date from December 1, 2018-December 31, 2020. Non-inferiority will have a margin set to the upper limit of 5% for serious AEs, and a lower limit of 5% for OS. To assess for safety, we are following up on AEs until end of patient’s Kaiser Permanente (KP) membership, death, six months after last rituximab dose, or December 2022 for all AEs except infusion reactions. For infusion reactions only, the follow up is 1 day. To assess for efficacy, we are following up on OS until end of patient’s KP membership, death, December 2022, or two years. Results: 535 patients were enrolled; 240 patients received RP rituximab and 295 patients received rituximab-abbs. The median time of follow up was 730 days, or 2 years (range in days, 2.0-730). Complete response was similar in the RP rituximab group and the rituximab-abbs group (70.4% vs. 77.3% respectively, p = 0.07). Additionally, partial response was also similar among the two products (19.2% vs. 16.9%, p = 0.51). The Kaplan-Meier two-year survival curve was also similar between the two products (p = 0.52), demonstrating no difference. Further statistical analysis confirmed the non-inferiority of the biosimilar products for survival. Infusion reaction adverse events (13.8% vs. 11.2%, p = 0.37) and non-infusion adverse events (68.3% vs. 71.2%, p = 0.47) were also similar in the two groups, with a survival curve demonstrating no difference between the two products and data analysis meeting the non-inferiority criteria. Conclusions: Rituximab and rituximab-abbs are non-inferior to each other in both efficacy and safety. Long term follow up would be needed to confirm these results.
Targeting regeneration capacity of stem cells to improve surgical wound healing outcomes in ovarian cancer patients.
Authors: Rebeca Kelly, Michelle Buchbinder, Diego Aviles, Krystal Hunter, Olga Ostrovsky
Journal: Journal of Clinical Oncology (2023)

e17578 Background: Despite advancements in care and treatment, ovarian cancer continues to be a challenging and deadly disease. Currently, standard treatment comprises a combination of cytoreductive surgery, often followed by platinum-based chemotherapy, known to negatively affect wound healing recovery. Therefore, achieving optimal post-surgical wound healing is critical in preventing delays in treatment, which can greatly impact patient outcomes and overall survival. Adipose-derived stem cells (ASC) have been shown to be crucial in regeneration of tissue and wound closure, as well as in regulating inflammatory differentiation and proliferation processes. Thus, improving the regeneration capacity of ASCs in wounds may speed post-surgical recovery and subsequent treatments. While a number of compounds have been shown to potentiate the regeneration ability of ASCs, we hypothesize that naturally derived epigenetic compounds with anti-cancer properties (I3C and EGCG), as well as anti-inflammatory compounds (non-psychoactive cannabidiol, CBD), may have a role in increasing regeneration capacity of stem cells. Therefore, ASCs were primed with these compounds and expression of major inflammatory, anti-inflammatory, proliferation and regeneration markers was evaluated. Methods: ASCs were primed with either I3C 50uM, EGCG 10 uM, or CBD 100nM. Conditioned medium from these treatments was collected and underwent a protein array assay for detection of levels of 40 human inflammatory markers and cytokines according to the manufacturer instructions. A one-way ANOVA test and Tukey post-hoc testing analyzed intensities for each marker between the control group and each of the primed groups. Results: Our results indicate that ASCs primed with our epigenetic treatments significantly decrease expression of a multitude of inflammatory markers and cytokines. I3C primed ASCs showed significantly decreased expression of the following factors: I-309, IL-11, IL-12 p40, IL-12p70, IL-1α, IL-6sR, M-CSF, MIG, MIP-1α, MIP-1β, MIP-1δ, IL-6, MCP-1, TIMP-2. EGCG primed ASCs significantly decreased expression of IL-12p70, IL-13, IL-6sR, MIP-1α, MIP-1δ, RANTES, IL-6, IL-8, MCP-1, TIMP-2. CBD primed ASCs significantly decreased expression of IL-6. A p&lt; .05 was used. Conclusions: Priming ASCs with EGCG, I3C and CBD significantly down-regulate expression of a number of pro-inflammatory markers known to delay and interfere with the kinetics of wound healing processes, including wound inflammation, closure and scar formation. Therefore, these results suggest that naturally derived epigenetic compounds and CBD successfully potentiated ASCs’ ability to attenuate inflammation and wound healing processes. Consequently, our findings can lead to new diet and surgical ASC protocols which could optimize cancer post-operative wound healing closure time while decreasing inflammation.
CT radiomic signature to predict overall survival and chemotherapy benefit in stage I and II HPV-associated oropharyngeal carcinoma.
Authors: Bolin Song, Kailin Yang, Vidya Sankar Viswanathan, Jonathan Lee, Sarah Stock, Pingfu Fu, Nabil F. Saba, Shlomo A. Koyfman, James S. Lewis, Anant Madabhushi
Journal: Journal of Clinical Oncology (2023)

6073 Background: Chemoradiation is the standard of care for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). However, not all patients would benefit from chemotherapy, especially patients with low-risk characteristics. We aim to develop and validate a prognostic and predictive radiomic image signature (pRiS) to inform survival and chemotherapy benefit in stage I and stage II HPV-associated OPSCC. Methods: Radiographic scans for 491 patients with stage I and stage II HPV-associated OPSCC were acquired from 4 independent sources and divided into three cohorts D 1 -D 3 . D 1 comprised computed tomography (CT) scans from 60 radiotherapy treated patients and was used to identify prognostic features via a LASSO Cox model to predict overall and disease-free survival. The prognostic performance of pRiS was evaluated on two test sets (D 2 , n = 162; D 3 , n = 269) using concordance index (C-index). An integrated nomogram was developed to demonstrate the incremental value of the pRiS to the existing clinical factors for individualized survival estimation. Patients from D 2 and D 3 who received either radiotherapy alone or chemoradiation were used to validate pRiS as predictive of added benefit of chemotherapy. Results: Seven radiomic features were selected to construct the image biomarker pRiS, which was found to be prognostic of overall survival (OS) on univariate analysis in D 2 (hazard ratio [HR] = 2.14, 95% confidence interval [CI], 1.1–4.16, p = 0.02) and D 3 (HR = 2.74, 95% CI, 1.34–5.62, p = 0.006). Chemotherapy was associated with improved OS for high-pRiS patients in both D 2 (radiation vs chemoradiation, HR = 4.47, 95% CI, 1.73–11.6, p = 0.002) and D 3 (radiation vs chemoradiation, HR = 2.99, 95% CI, 1.04–8.63, p = 0.04). In contrast, chemotherapy did not improve OS for low-pRiS patients, which indicates these patients did not derive additional benefit from chemotherapy and could be considered for treatment de-escalation. Conclusions: The proposed radiomic signature was prognostic of patient survival and the binary pRiS group informed chemotherapy benefit for stage I and II HPV-associated OPSCC patients. [Table: see text]